Tribbles homolog 2 (Trib2) and HoxA9 cooperate to accelerate acute myelogenous leukemia

• Published in: Blood cells, molecules, & diseases Vol. 40; no. 1; pp. 119 - 121
• Main Authors: Keeshan, Karen, Shestova, Olga, Ussin, LaShon, Pear, Warren S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2008
• Subjects: Animals; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - metabolism; Homeodomain Proteins - administration & dosage; Homeodomain Proteins - pharmacology; Intracellular Signaling Peptides and Proteins - administration & dosage; Intracellular Signaling Peptides and Proteins - pharmacology; Leukemia, Myeloid, Acute - etiology; Leukemia, Myeloid, Acute - pathology; Mice; Oncogene Proteins; Protein-Serine-Threonine Kinases - administration & dosage; Protein-Serine-Threonine Kinases - pharmacology; Transduction, Genetic
• ISSN: 1079-9796; 1096-0961
• DOI: 10.1016/j.bcmd.2007.06.005

Trib2 is a member of the Trib family of serine/threonine kinase-like proteins (Trib1, Trib2, Trib3). Mice reconstituted with hematopoietic stem cells (HSC) retrovirally expressing Trib2 uniformly developed fatal transplantable acute myelogenous leukemia (AML). Trib2-induced AML was clonal and we sought to identify cooperating genes in Trib2-induced AML. Using Splinkerette PCR techniques, we identified proviral insertion near HoxA9 in a Trib2 monoclonal tumor, which resulted in greatly elevated HoxA9 expression. Mice reconstituted with HSC cotransduced with HoxA9 and Trib2 had accelerated onset of AML compared to either gene alone. These data identify Trib2 and HoxA9 as cooperating genes in AML.